Abstract
SCOPE: Stress is a known contributor to various forms of disease in humans and animals, although mechanisms are still unknown. In animals, psychosocial stress-induced depression/anxiety phenotypes are coincidental with increased inflammation in both brain and blood. The authors recently showed that a novel treatment with a select bioactive polyphenol preparation promotes resilience to stress-mediated depression/anxiety phenotypes mice. Moreover, selective bioactive phenolic compounds within the polyphenol preparation are identified that are effective in mitigating the behavioral effects of bone marrow transplantation from stressed mice. METHODS AND RESULTS: Here, an animal model of adult stress and bone marrow transplantation is used to identify an epigenetic signature of repeated social defeat stress (RSDS) that is passed through bone marrow hematopoietic progenitor cells to naïve mice, revealing the maintenance of epigenetic memory following stress both centrally and peripherally. Further, polyphenols are administered to naïve and stress-susceptible mice, demonstrating that polyphenol treatment in mice from both susceptible and naïve donors alters global DNA methylation in the central nervous system and periphery and likewise has an effect on human blood cells after immune challenge. CONCLUSIONS: Findings highlight the enduring molecular memory of stress and the possible mechanism by which select bioactive polyphenols may promote resiliency to stress. Polyphenols may be an efficacious alternative to traditional pharmacological treatments in psychiatry.